OnCo
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Neoadjuvant checkpoint inhibitor → surgery (or no surgery) in dMMR colorectal cancer

Test the tumour for a broken DNA spell-checker; if it has one, immunotherapy before surgery melts most tumours and in the rectum can replace surgery altogether.

NICHE-2 (colon: 68% pCR, 100% 3-year DFS after 4 weeks of nivolumab + ipilimumab), the MSK dostarlimab rectal cohort and AZUR-1 (organ preservation), and ATOMIC (adjuvant atezolizumab, DFS HR 0.50). Universal MMR/MSI testing at diagnosis is the gate.

Rationale
dMMR tumours carry thousands of frameshift neoantigens and respond to checkpoint blockade far more than chemotherapy; a primary tumour in situ provides antigen for priming.
Evidence
Phase 2 single-arm (NICHE-2, AZUR-1) and phase 3 adjuvant (ATOMIC).

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